Background: Air pollution is linked to low lung function and to respiratory events, yet little is known of associations with lung structure. Objectives: We examined associations of particulate matter (PM(2.5,) PM(10)) and nitrogen oxides (NO(x)) with percent emphysema-like lung on computed tomography (CT). Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited participants (45–84 years of age) in six U.S. states. Percent emphysema was defined as lung regions < –910 Hounsfield Units on cardiac CT scans acquired following a highly standardized protocol. Spirometry was also conducted on a subset. Individual-level 1- and 20-year average air pollution exposures were estimated using spatiotemporal models that included cohort-specific measurements. Multivariable regression was conducted to adjust for traditional risk factors and study location. Results: Among 6,515 participants, we found evidence of an association between percent emphysema and long-term pollution concentrations in an analysis leveraging between-city exposure contrasts. Higher concentrations of PM(2.5) (5 μg/m(3)) and NO(x) (25 ppb) over the previous year were associated with 0.6 (95% CI: 0.1, 1.2%) and 0.5 (95% CI: 0.1, 0.9%) higher average percent emphysema, respectively. However, after adjustment for study site the associations were –0.6% (95% CI: –1.5, 0.3%) for PM(2.5) and –0.5% (95% CI: –1.1, 0.02%) for NO(x). Lower lung function measures (FEV(1) and FVC) were associated with higher PM(2.5) and NO(x) levels in 3,791 participants before and after adjustment for study site, though most associations were not statistically significant. Conclusions: Associations between ambient air pollution and percentage of emphysema-like lung were inconclusive in this cross-sectional study, thus longitudinal analyses may better clarify these associations with percent emphysema. Citation: Adar SD, Kaufman JD, Diez-Roux AV, Hoffman EA, D’Souza J, Stukovsky KH, Rich SS, Rotter JI, Guo X, Raffel LJ, Sampson PD, Oron AP, Raghunathan T, Barr RG. 2015. Air pollution and percent emphysema identified by computed tomography in the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 123:144–151; http://dx.doi.org/10.1289/ehp.1307951